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Methoxsalen (ECP) versus drug combination for steroid‑refractory immune‑related colitis or hepatitis in metastatic melanoma on checkpoint therapy

Verified siteRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

The study focuses on patients with advanced skin cancer called melanoma who have developed inflammation of the colon (immune-related colitis) or liver (immune-related hepatitis) after receiving cancer drugs known as immune checkpoint inhibitors. These inflamed conditions have not improved enough with corticosteroids, which are medicines that lower swelling. The trial is testing whether a procedure called extracorporeal photopheresis can help these patients stop needing steroid medicines. The purpose of the study is to evaluate how well this procedure works compared with other commonly used medicines such as azathioprine, vedolizumab, infliximab, mycophenolate mofetil, and methoxsalen.

Participants are randomly assigned to receive either the photopheresis therapy or one of the standard medicines. In the photopheresis arm, blood is drawn, mixed with a light‑sensitive drug, exposed to ultraviolet light, and then returned to the body, usually once or twice a week for several weeks. In the other arm, patients take or receive the standard medicines by mouth or through an IV according to usual practice. All participants are followed for about three months with regular check‑ups and lab tests to see if their colon or liver inflammation improves and if they can stop steroid use, while safety is monitored throughout the study.

The research process

The trial runs in 7 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Baseline visit and randomization

    After joining the study, you will have a baseline visit where medical history, physical exam, and laboratory tests are recorded.

    Based on the results, you will be randomly assigned to receive either extracorporeal photopheresis (ecp) or the best available therapy (bat).

  2. Step 2

    Start of ecp treatment (if assigned to ecp arm)

    The ecp procedure involves removing a portion of your blood, treating it with a drug called methoxsalen and ultraviolet a light, and then returning it to your body.

    Each ecp session uses methoxsalen at a dose of 10 ml administered extracorporeally.

    Sessions are scheduled according to the study protocol and continue for up to 12 weeks.

  3. Step 3

    Administration of best available therapy medications (if assigned to bat arm)

    You may receive one or more of the following medicines, each given at the dose shown:

    azathioprine: 2 mg per kilogram of body weight taken by mouth each day.

    vedolizumab: 300 mg given by intravenous infusion, frequency determined by the investigator.

    infliximab: 5 mg per kilogram of body weight given by intravenous infusion, frequency determined by the investigator.

    mycophenolate mofetil: 2 g taken by mouth each day.

    These drugs are continued for the 12‑week treatment period unless stopped for safety reasons.

  4. Step 4

    Weekly monitoring visits

    You will attend a clinic visit approximately every week during the first 12 weeks.

    At each visit, blood tests, assessment of colitis or hepatitis symptoms, and recording of any side effects are performed.

    The investigator will evaluate your response using standard criteria and may adjust medication doses as needed.

  5. Step 5

    Week 12 assessment

    At the end of week 12, a formal evaluation is performed to determine whether the immune‑related colitis or hepatitis has improved without the need for corticosteroids.

    The assessment includes clinical examination, laboratory tests, and documentation of any adverse events.

  6. Step 6

    Week 13 follow‑up (colitis specific)

    If you have colitis, an endoscopic examination is performed to check the modified mayo subscore and to collect tissue for histological analysis.

    The goal is to confirm any improvement observed at week 12.

  7. Step 7

    Post‑treatment safety follow‑up

    After the last ecp session or the final dose of best available therapy, you will be monitored for an additional 30 days.

    During this period, any new symptoms or delayed side effects are recorded and reported to the study team.

Who can join the trial?

14 criteria

  • Be fully informed about the study, understand its risks, and be able to sign the informed consent form.
  • Have an ECOG performance status of 0, 1, or 2 (a simple scale that shows how well you can perform daily activities, where 0 means fully active and 2 means able to care for yourself but not able to work).
  • Have a life expectancy longer than 4 months.
  • Have a suitable vein (either a regular vein or a special central line) that can be used for the ECP treatment, known as adequate peripheral or central venous access.
  • Be either unable to become pregnant (non‑childbearing potential) or be using a highly effective method of contraception (birth control).
  • If your sexual partner could become pregnant, you must use condoms or another reliable form of contraception and avoid donating blood, semen, or sperm during the study and for 90 days after the last treatment.
  • Agree to follow all study procedures and be available for the entire study period.
  • Be an adult (age ≥ 18 years), any sex or gender.
  • Have a diagnosis of melanoma that cannot be removed by surgery or has spread to other parts of the body (unresectable or metastatic melanoma, stage III or IV).
  • Have received immune checkpoint inhibitors (ICI) (cancer drugs that help the immune system, such as anti‑PD‑1, anti‑PD‑L1, anti‑LAG‑3, or anti‑CTLA‑4), either alone or in combination.
  • Your ICI treatment was paused or stopped because you developed immune‑related colitis or hepatitis (ir‑colitis or ir‑hepatitis).
  • You have been diagnosed with ir‑colitis or ir‑hepatitis that is at least Grade 2 in severity (meaning the symptoms are more than mild, according to cancer‑treatment guidelines).
  • If you have colitis, a colonoscopy performed within 10 days before randomization must show clear evidence of the condition (endoscopic evidence of ir‑colitis).
  • You have not responded adequately to corticosteroids, which means either no improvement after at least 72 hours of steroid treatment (corticosteroid‑refractory) or the symptoms returned to Grade 2 or higher when the steroids were reduced (corticosteroid‑dependent).

Who cannot join the trial?

24 criteria

  • Having other immune‑related side effects that are more severe than the colitis or hepatitis being studied, as judged by the ASCO guidelines (a set of rules doctors use to grade side effects).
  • Being allergic to any part of the medicines 8‑methoxsalen, infliximab, vedolizumab, MMF, or azathioprine.
  • Having aphakia (missing the eye lens) or a history of light‑sensitive diseases such as lupus, porphyria (a group of disorders that affect skin and blood), xeroderma pigmentosum, or albinism.
  • Being unstable in blood circulation, needing medicines called vasopressors to keep blood pressure up, or having severe heart failure (New York Heart Association class III or IV), uncontrolled high blood pressure, or dangerous heart rhythm problems.
  • Being unable to handle the fluid changes that occur during the ECP (extracorporeal photopheresis) procedure.
  • Having a history of HIV infection or a positive HIV test.
  • Testing positive for tuberculosis (TB) in a blood test.
  • Testing positive for active or past hepatitis B or for active hepatitis C.
  • Testing positive for the viruses Epstein‑Barr (EBV), cytomegalovirus (CMV), or adenovirus.
  • Having an active COVID‑19 infection.
  • Having had a previous allogeneic bone‑marrow transplant or any solid‑organ transplant.
  • Having only uveal melanoma (eye melanoma) without any skin, nail, or mucosal melanoma.
  • Having any other active cancer besides the unresectable or metastatic melanoma being studied.
  • Having had a splenectomy (surgical removal of the spleen).
  • Being treated at the same time with another experimental drug, device, or intervention.
  • Having any condition that the doctor believes would stop you from fully taking part in the study, make the study unsafe, or affect the study results.
  • Being unable to use a smartphone or other electronic device to fill out study diaries and questionnaires.
  • Being treated for the colitis or hepatitis with any systemic therapy other than corticosteroids.
  • Having a condition that requires high‑dose corticosteroids (more than 1 mg per kilogram of body weight per day), which would interfere with the planned steroid taper.
  • Having pre‑existing liver disease such as autoimmune hepatitis, primary sclerosing cholangitis, or primary biliary cholangitis.
  • Having an active alcohol use disorder (problematic drinking) as judged by the doctor.
  • Receiving chemotherapy or targeted therapy for melanoma at the same time.
  • Having used any investigational (experimental) drug within five half‑lives (the time it takes for half the drug to leave the body) before randomization.
  • Having any known contraindication (reason it should not be used) to the study medicines or procedures, including methoxalen, the ECP procedure, infliximab, vedolizumab, MMF, or azathioprine.
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Investigated drugs

  • Extracorporeal Photopheresis (ECP)

    is a treatment that takes a small amount of blood out of the body, mixes it with a light‑sensitive medicine called methoxsalen, and then shines a special type of ultraviolet (UVA) light on the mixture. After the light exposure, the blood is returned to the patient. This process helps calm an over‑active immune system that is causing inflammation of the colon (colitis) or liver (hepatitis) in people who have melanoma and are being treated with immune checkpoint inhibitors.

  • Azathioprine

    is a pill taken by mouth that weakens the immune system. By doing so, it reduces the inflammation that can occur in the gut or liver when other treatments have not been enough.

  • Vedolizumab

    is given through an IV (a needle in a vein). It works by blocking a specific protein on immune cells, which stops these cells from entering the gut. This helps lower gut inflammation and improves symptoms of colitis.

  • Infliximab

    is also given by IV infusion. It is a type of antibody that targets a substance called tumor necrosis factor‑alpha (TNF‑α), which plays a key role in causing inflammation. By blocking TNF‑α, infliximab helps reduce severe inflammation in the colon.

  • Mycophenolate mofetil

    is an oral medication that limits the growth of certain immune cells. This action weakens the overall immune response, helping to control inflammation in the liver or gut when other therapies are not fully effective.

What is already known about the treatment

  • Azathioprine

    This medication is taken by mouth in tablet form, usually dosed by body weight. It is an approved drug that has been used for many years to treat organ‑transplant patients and several autoimmune diseases. It works by being changed inside the body into a compound that blocks DNA building blocks, which reduces the activity of immune cells. It belongs to the antimetabolite class of immunosuppressants.

  • Vedolizumab

    Vedolizumab is given as an intravenous infusion, typically once every few weeks. It is a licensed biologic medicine used mainly for ulcerative colitis and Crohn’s disease. The drug attaches to a protein called α4β7 integrin on immune cells, stopping them from entering the gut and causing inflammation. It is classified as a selective adhesion‑molecule antagonist (a monoclonal antibody).

  • Infliximab

    Infliximab is administered by intravenous infusion, usually at a dose based on body weight. It is an approved treatment for several inflammatory conditions such as Crohn’s disease, ulcerative colitis, and rheumatoid arthritis. The medication binds to the inflammatory protein TNF‑alpha, neutralizing its effect and calming the immune response. It is categorized as an anti‑TNF biologic agent.

  • Methoxsalen

    Methoxsalen is supplied as a liquid solution that is added to blood outside the body during extracorporeal photopheresis, after which the blood is exposed to UVA light. It is an authorized drug used in phototherapy for skin disorders and in extracorporeal photopheresis for immune‑mediated conditions. When activated by UVA, it inserts itself into DNA and creates cross‑links that suppress the activity of immune cells. It is classified as a psoralen‑type immunomodulator.

  • Mycophenolate mofetil

    This drug is taken orally as tablets, with the dose often measured in grams per day. It is an approved medication for preventing organ‑transplant rejection and for some autoimmune diseases. It blocks an enzyme needed to make guanine nucleotides, which limits the growth of lymphocytes that drive immune reactions. It belongs to the antimetabolite class of immunosuppressive agents.

Investigated diseases

  • Immune‑related colitis

    This is inflammation of the colon that occurs as a side effect of immune checkpoint inhibitor therapy. It typically begins with mild diarrhea and abdominal cramping and can worsen to frequent watery stools, blood in the stool, or severe pain. If the inflammation continues, the lining of the colon becomes increasingly damaged, leading to ulcer formation. Persistent inflammation may cause narrowing of the colon and impaired nutrient absorption. The condition evolves from mild irritation to more extensive colonic injury if not controlled.

  • Immune‑related hepatitis

    This is inflammation of the liver triggered by immune checkpoint inhibitor treatment. Early signs include mild fatigue and slight elevation of liver enzymes detected on blood tests. As the inflammation progresses, patients may develop jaundice, abdominal discomfort, and higher enzyme levels. Ongoing injury can lead to swelling of liver tissue and reduced liver function. Without resolution, the inflammation can spread, affecting larger portions of the liver and worsening overall health.

Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IITrial ID2026-526261-14-00Protocol codeTKS2001Estimated enrolment112 patients

sourced from the EU Clinical Trials Register and site verification

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